Fully acetylated sugar acids and processes for their production



I Patented 30,

assess:

PATENT OFFlCE FULLY scam-ran SUGAR ACIDS AND raocassss FOR 'rncmPRODUCTION Randolph 1. Major, Plainfleld, N. 1., and Elmer .W. 'Cook,New York, N. Y., assignors toMerck d: 00., Inc'., Rahway, N. .L,

New Jerk! No nmvinr. Original at I corporation of application December23,

o 1936, Serial No.'1l7,336. Divided and this al plication March 8,1939,Serial No. 260,586

6 Claims. (c1. 26o 4ss) This is a division of application Serial No.117,336, filed December 23, 1936. v

This invention relates to fully acetylated sugar acids and to processesfor their production.

The 2-keto-sugar acids'have recently acquired considerable interest inview 'of the fact that the enol forms of the lactonesfrom these acidshave been shown to be vitamin C and its homologs. (Hirst, Chemistry andIndustry, 1933, p. 221, and Haworth, Chemistry and Industry, 193 482.)

We have discovered a new method of preparing the acetyl derivatives of2-keto sugar acids which involves the use of fully acetylated acids asstarting materials.

- According to our improved process, the selected fully acetylated sugaracid is first converted to its acyl chloride, which is converted to thecorresponding nitrile, and from this nitrile the corresponding 2-ketoacid is obtained by hydrolysis.

In the following examples we are illustrating the steps of our processas applied specifically to pentaacetyl-d-gluconic acid andtetraaceytl-d, l-xylonic acid:

FULLY ACETYLATED SUGAR ACID ACYL CHLORIDES The dry fully acetylatedsugar acid is added with cooling to a suspension of one molecularequivalent of phosphorous pentachloride in ten times its weight of dryether. The reaction is soon completed, as shown by the disappearance ofthe phosphorous pentachloride.

Pentaacetyl-d-yluconyl chloride After. the solution has stood at roomtemperature for 2 or 3 hours, the ether is evaporated in vacuo. Dryxylene is then added. This and the phosphorous oxychlorlde formed in thereaction are removed by evaporation at 45 to 50 C., in vacuo. Theaddition of xylene. followed by evaporation in vacuo, is repeated twice.The residual gum is dissolved in dry ether. Upon evaporation in a slightvacuum, beautiful white crystals separate. They have a melting point of6870, and (a) +2 (dry chloroform, 0,2).

With water, the acid chloride gives pentaacetyI-d-gluconic acidmonohydrate.

Tetraacetyl-dJ-xylonyl chloride White crystals appear soon aftersolution of the phosphorous pentachloride. The precipitate isrecrystallized from dry ether. The product has a melting point of 90-92,and 0" (dry chloroform; c,2).

' FULLY Acs'rYLArsp 2-Ks'r0 SUGAR ACID NrrnnasPentaacetyl-Z-keto-d-glucoheptonitrile About gms. ofpentaacetylgluconyl' chloride I 5 are heated for one hour with 4.7 gms.of silver cyanide in a closed tube at 120-125 C. The fused contents arefrequently shaken to insure good contact of the acid chloride with thesilver cyanide. After cooling, the gummy material is thoroughlyextracted with anhydrous ether and filtered from the silver salts.Petroleum ether is added carefully to precipitate a part of the productas a dark colored syrup, thereby removing most of the color. Then anexcess of petroleum ether is added with cooling.' A gum is precipitatedalong with some crystalline product. The supernatant liquor is pouredofl and on evaporation yields crystalline pentaacetyl-2-keto-d-glucoheptonitrile. The gum is dissolved in a small quantity ofabsolute alcohol and upon standing in an ice box for 24 hours yields aquantity of pentaacetyl-Z-keto-glucoheptonitrile. The product ispurified by recrystallizing it from absolute alcohol. It has a meltingpoint of 116, 25 and =+7 (dry chloroform, 0,2).

When this compound is heated in water with either dilute acid or a base,hydrogen cyanide is evolved.

Tetraacetyl-Z-keto-d,l-gulononitrile This nitrile is prepared in thesame way as pentaacetyl 2 keto d glucoheptonitrile, ex-

cept that the filtrate obtained after the addition of sufilcientpetroleum ether to the ether extract to produce slight turbidity, istreated with another larger portion of petroleum either whichprecipitates a gum. Trituration of this gum with absolute alcohol yieldsa solid precipitate. It is recrystallized from alcohol, and has amelting point of 125-126".

FULLY ACETYLATED 2-Ksro SUGAR ACIDS ,Pentaacetyl-Z-keto-d-glucoheptonicac id About 7.55 gms. of pentaacetyl-2-keto-d-glucoheptonitrile aredissolved in 20 cc. of pure dioxane. To this, about 13.1 cc. of 1.39 nhydrogen chloride in dioxane is added. The solution is cooled and 0.33cc. of water is added. The solution is allowed to stand for another 24hours, by which time ammonium chloride precipitates. Ether is added andthe ammonium chloride filtered. The filtrate is evaporated in vacuo to agum. The gum is dissolved in ether andevaporation in vacuo is repeated.The remaining gum crystallizes on scratching. It has a melting point of136-138. After recrystallization from water it melts at'160-161, (al 0(alcohol, 0,2) A solution of the keto acid in water is acid to congo redpaper. It is extremely soluble in alcohol, ether, chloroform, andacetone.

Esrrzns or FULLY Acs'rrmrsn z-Ks'ro SUGAR Acms Ethylpentqacetul-Z-keto-d-glucoheptonate 97-98, (11):):0 (alcohol; 0,2).

Methyl tetraacetyl-Z-keto-d-gluconate -About 1 gram ofmethyl-2-keto-d-gluconate is added to 5 cc. of acetic anhydrldecontaining 0.4 gm. of zinc chloride at 0. As soon as solution iscomplete (about 30 minutes) the mixture is allowed to come to roomtemperature and remain there for 24 hours. It is then poured into 25 cc.of ice water. A white solid separates. It is recrystallized fromabsolute alcohol and has a melting point of 168-169 and (a) =--133,(chloroform; 0,2).

From the foregoing description of the detailed steps 01' our newprocess, it will be apparent to those skilled in the art thattetraacetyl-Z-ketoulononitrile can be similarly hydrolyzed to thecorresponding tetraacetyl-Z-keto-gulonic acid iii and that this may besubsequently esterifled, all in accordance with the steps described forthe production of the corresponding 2-keto-glucoheptonic acid and itsderivatives.

We claim as our invention:

1. Fully acetylated 2-keto-sugar acids.

2. Pentaacetyl-2-keto-d-glucoheptonic acid.

3. Tetraacetyl-2-keto-gulonic acid.

4. Process for the production of acetylated 2- keto-sugar acids fromfully acetylated sugar acids which comprises preparing the acyl chlorideof the fully acetylated sugar acids-converting the acyl chlorides intothe corresponding nitriles, and hydrolyzing the latter to give thecorresponding 2-keto-sugar acids. 4

5. Process for the production of pentaacetyl-2- keto-glucoheptonic acidwhich comprises treating anhydrous pentaacetyl gluconic acid withphosphorous pentachloride, reacting upon the chloride thus obtained withsilver cyanide, and converting the resultingpentaacetyl-2-keto-d-gluco-heptonitrile to pentaacetyl 2keto-d-glucoheptonic acid, by hydrolysis.

6. Process for the production of tetraacetyl-2- keto-gulonic acid whichcomprises treating tetraacetyl-d-l-xylonic acid with phosphoroupentachloride, reacting upon the acylchloride thus obtained with silvercyanide, and converting the resulting tetraacety1-2-keto-d lgulononitrile to tetraacetyl-2-keto-gulonic acid by hydrolysis.

RANDOLPH T. MAJOR. ELMER W. COOK.

